Takeda Chemical Industries, Inc.

Chitoshi Hatanaka

Kanji Meguro

Takeshi Fujita

Satoru Oi

Satoru Ooi

Masahiko Fujino

Mitsuhisa Yamano

Yasuaki Abe

Sigel Nuwa

Method for producing peptides and their salts which have an agonist activity of luteinizing hormone releasing hormones secreted from the hypothalamus

There is disclosed an improved process for substitution of the hydroxy group at 2-position of an ascorbic acid derivative according to the following reaction scheme: ##STR1## wherein R.sup.0 is hydrogen, alkyl having 1 to 6 carbon atoms, phenyl or a group of the formula ##STR2## (wherein X is two hydrogen atoms, or acetal or ketal residue); R.sup.1 is an alkyl or alkenyl group having up to 22 carbon atoms which may be substituted with phenyl or alkoxy having 1 to 22 carbon atoms; Y is halogen or optionally substituted sulfonyloxy; R is hydrogen, or primary, secondary or tertiary alkyl having 1 to 10 carbon atoms; and Z is an alkali metal or an alkali earth metal. There is also disclosed hydrolysis of the following scheme: ##STR3## wherein R.sup.1 is as defined above; and X is acetal or ketal residue.

Selective etherification

An improved process for producing a substituted vinyl pyridine compound of the general formula: ##STR1## wherein R.sup.1 is pyridyl group; R.sup.2 is an optionally substituted aromatic or heterocyclic group; R.sup.3 is a lower alkyl group, hydroxymethyl group, nitroxymethyl group, a nitrogen containing 5 membered ring-methyl group, an acetal-methyl group, a trialkylsilyloxymethyl group, an alkyl- or aryl-sulfonyloxymethyl group, an alkyl- or aryl-sulfonylaminocarbonyloxymethyl group, an acyloxymethyl group, an alkoxycarbonyloxymethyl group, a halogenomethyl group, an alkoxymethyl group, an aryl-oxymethyl group, cyano group, an optionally substituted carbamoyl group, an optionally substituted carbamoyloxymethyl group, an optionally substituted thiocarbamoyloxymethyl group, carboxyl group or an alkoxycarbonyl group; and n is an integer of 1 to 22, which comprises reacting a compound of the general formula: ##STR2## wherein R.sup.1 and R.sup.2 are as defined above, with a compound of the general formula:

Process for producing substituted vinyl pyridine derivatives

A compound of the formula: ##STR1## (wherein R.sup.1 is hydrogen or a lower alkyl) can be produced advantageously by (1) reacting a compound of the formula: ##STR2## (wherein R.sup.1 has the meaning given above) with a halogenating agent or sulfonyl halide to give a compound of the formula: ##STR3## (wherein R.sup.1 has the meaning given above and X is a halogen or an alkyl- or aryl-sulfonyloxy), (2) reacting the resulting compound with a compound of the formula: ##STR4## to give a compound of the formula: ##STR5## (wherein R.sup.1 has the meaning given above), (3) reacting the resulting compound with a compound of the formula: ##STR6## to give a compound of the formula: ##STR7## (wherein R.sup.1 has the meaning given above), and (4) subjecting the resulting compound to catalytic reduction.

Pyridine and thiazolidinedione derivatives

A compound of the formula: ##STR1## (wherein R.sup.1 is hydrogen or a lower alkyl) can be produced advantageously by (1) reacting a compound of the formula: ##STR2## (wherein R.sup.1 has a meaning given above) with a halogenating agent or sulfonyl halide to give a compound of the formula: ##STR3## (wherein R.sup.1 has a meaning given above and X is a halogen or an alkyl- or aryl-sulfonyloxy), (2) reacting the resulting compound with a compound of the formula: ##STR4## to give a compound of the formula: (wherein R.sup.1 has the meaning given above), (3) reacting the resulting compound with a compound of the formula: ##STR5## to give a compound of the formula: ##STR6## (wherein R.sup.1 has the meaning given above), and (4) subjecting the resulting compound to catalytic reduction.

Method for producing thiazolidinedione derivatives

Crystalline thyrotropin releasing hormone (TRH) tartrate was obtained for the first time from a solution comprising TRH, tartaric acid and a certain solvent. The crystals are very pure and very stable against moisture for a long period of time.

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Nagaokakyo, Japan

Chitoshi Hatanaka